Despite known risks, opioids are widely used for chronic non-cancer pain (CNCP). Clinical guidelines now recommend deprescribing, but factors predicting success are poorly understood. This systematic review aimed to identify clinician and patient factors associated with attaining successful opioid dose reduction or discontinuation in adults with CNCP. We searched major electronic databases on 18 March 2025 for observational studies evaluating factors associated with opioid reduction in deprescribing interventions, excluding studies on cancer/palliative care or primary substance use disorder. The primary outcome was the association between clinician- or patient-related factors and opioid reduction/discontinuation. Two reviewers independently screened studies, extracted data, and assessed bias using the ROBINS-I tool. A narrative synthesis was conducted as there was significant heterogeneity between studies which did not allow for a meta-analysis. Thirty-two studies (n = 26 retrospective cohorts) were included. Evidence on clinician factors was limited, though one study found that a documented deprescribing plan was associated with greater opioid dose reduction (aOR: 3.63, 95% CI: 2.96-4.46). Among patient factors, higher baseline dose and longer duration of opioid use were associated with a lower likelihood of opioid discontinuation in four high-quality studies. Findings for other factors (e.g., age, mental health) were conflicting. Certainty was low due to methodological limitations, with 19 studies having a serious risk of bias. In conclusion, a documented deprescribing plan was the most promising modifiable factor. While long-term opioid use is a consistent barrier, inconsistent evidence for other patient-level factors reinforces the need for individualized care. Future high-quality research should focus on clarifying inconsistent findings and addressing the critical evidence gap regarding clinician and health system-level factors (PROSPERO: CRD42021270488).
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